Iron and Haem Metabolism Flashcards
describe the structure of haemoglobin
Haemoglobin is composed of:
4 globin molecules which provide a waterproof pocket in which sit the 4 haem elements.
Haem is composed of a porphyrin ring and an integral Fe2+
Iron within this complex is important because it binds to O2
This binding is reversible because of the way the Fe2+ interacts with the globin molecule
describe the body’s need for iron
Iron is the second most abundant metal on earth but lack of it is still the World’s most common cause of anaemia
1-3g on average stored in the body and used mainly in erythropoiesis (production of RBCs)
Requirement is increased when body mass is increased in the neonate and growth spurts in childhood.
Although ~1mg of iron is lost in the sloughing of cells from skin and mucosal surfaces and another 1mg per day can be lost through menstruation, there is no regulated excretion of iron from the body.
describe iron absorption
Intake is in the form of haem and non-haem: non-haem is harder to absorb
Iron absorption takes place mainly in the duodenum and the jejunum
Haem and non-haem iron are absorbed in different ways
In the stomach Fe3+ is reduced to Fe2+
Aided by e.g. Ascorbate, citrate
Inhibited by e.g. phytates, tannins
Fe2+ is then taken into the enterocytes a process which is regulated so the amount of fe2+ taken up is proportional to the amount needed by the body.
what effects dietary absorption of iron
effected by meal composition and can be affected by loss of stomach function – especially gastric acid production
describe iron transport and regulation
Mostly transported to bone marrow for erythropoiesis
Iron is transported out of the enterocyte into plasma by ferriportin
In the plasma it binds transferrin and is distributed round the body via the blood . Normally about 30% saturated.
The liver senses high body iron stores or low erythroid iron requirements and produces appropriate amounts of an inhibitory peptide, Hepcidin = key regulator of iron homeostasis, is important for maintaining constant levels.
describe iron storage
70% of iron in body is within haem of erythrocytes with a small amount in myoglobin
A small amount is available for use in the circulation as it is bound to transferrin in the plasma
The rest is stored as iron.
The main store of iron is in the liver- stored in hepatocytes bound to ferritin
when could there be iron overload
- Transfusion for chronic anaemias
- Hereditary haemochromatosis: excess iron absorption,
saturation of iron-binding proteins deposition of hemosiderin in the tissues. Iron accumulates in joints causing pain and increased risk of infections.
when could there be iron deficiency
Iron deficiency anaemia microcytic, hypochromic RBCs
Causes: excess menstral flow, GI bleeding
what are Porphyria’s?
Porphyria’s are a group (8 known to date) of disorders caused by the partial deficiency of one of the enzymes which drives each of the reactions in the Porphyrin ring. This leads to a build up of porphyrin or porphyrin precursors.
what are symptoms of acute porphria?
how can it be diagnosed?
episodes of severe pain especially abdominal, back and limbs; muscle weakness and in extreme cases neurological symptoms e.g. Anxiety, confusion, seizures
Most common diagnostic test of acute porphyrias is the measurement of phorphobilinogen in urine and plasma.
describe hyperbilirubimia/jaundice?
• Excess circulation and accumulation of bilirubin (hyperbilirubinemia) causes yellow-orange discolouration of tissues especially visible in whites of eyes
• Billirubin toxicity (encephalopathy) can be fatal in neonates and is characterised by yellowing of basal ganglion with extreme jaundice
• Was described over a century ago and termed ‘kernicterus’
• Defects in various steps of this pathway leads to various types of jaundice.
• The causes of jaundice are conventionally classified as:
o Prehepatic: increased production of bilirubin
o Intrahepatic: impaired secretion of bilirubin
o Posthepatic: obstruction to biliary drainage
describe prehaptic jaundice
Production of excess unconjugated bilirubin faster than liver can conjugate it for excretion
Bilirubin is not water soluble and cannot be excreted
Usually caused by haemolysis from eg homozygous sickle cell or thalassaemia major.
Also haemolytic disease of the newborn (Rh- or ABO- incompatibility
High plasma concentrations of unconjugated bilirubin (normal concentration ~0.5 mg/dL)
describe intrahepatic jaundice
Impairment of bile flow
Usually due to hepatocyte
Usually accompanied by other abnormalities in biochemical markers of liver function serum levels of the liver enzymes aspartate amino transferase (AST) and alanine aminotransferase (ALT) are elevated.
describe posthepatic jaundice
Caused by an biliary obstruction
Conjugated bilirubin is water soluble and excreted in urine giving it a dark colour (bilirubinuria
Also characterized by pale colored stools caused by lack of bilirubin entering the gut
In a complete obstruction, urobilinogen is absent from the urine
describe neonatal jaundice
Common, particularly in premature infants
Transient (resolves in the first 10 days)
Due to immaturity of the enzymes involved in bilirubin conjugation
High levels of unconjugated bilirubin are toxic to the newborn – due to its hydrophobicity it can cross the blood-brain barrier and cause a form of brain damage called kernicterus
Treatment usually phototherapy with UV light is used to convert it to a water soluble, non-toxic form
If necessary, exchange blood transfusion is used to remove excess bilirubin
